Chloramphenicol (CAP) resistance in mammalian cells has been shown to be cytoplasmically inherited by its ability to be transferred from resistant (R) to sensitive (S) cells via enucleated cell fragments (cybrid formation). Additional studies have demonstrated that mitochondria are incompatible in certain strains of the same species and that this incompatibility is paralleled by mouse RNA tumor virus host range. This raises the possibility that mitochondrial incompatibility and RNA tumor virus host range may be regulated by the same mechanism. To test this possibility, studies on mitochondrial compatibility types will be expanded and the mechanisms of incompatibility explored by both genetic and molecular approaches. Since malignant cells have been shown to have altered mitochondrial physiology, the effects of SV40 virus transformation on mitochondrial phenotype will also be examined. Additional studies will also be conducted on the arrangement of nuclear DNA and mitochondrial DNA-coded mitochondrial genes using interspecific and intraspecific hybrids and cybrids. It is hoped that the above experiments will provide insights into the regulation by the cell of mitochondria and tumor virus growth, the role of the mitochondria in maintenance of the transformed state, and the genetics of the mitochondria itself.